This study examined the impact of an interleukin-6 (IL-6) knockout on fracture healing in terms of histological and biomechanical responses. Following IACUC approval, tibial fractures were produced in 4-to 6-week-old IL-6 knockouts (n ¼ 35) and wild-type mice (n ¼ 36) and harvested along with contralateral limbs at 2 and 6 weeks postsurgery. Histology quantified stage of healing, lymphocyte infiltration, TRAPþ cells, and osteocalcin deposition. Bend testing established maximum load and stiffness. Based on normality assessments, Mann-Whitney U or independent t-tests were used for data analysis using a p-value threshold of 0.05. Stage of healing, lymphocyte infiltration, and osteocalcin deposition were similar for all time points (p ! 0.243). TRAPþ cell counts were reduced approximately 10-fold in the knockout at 2 weeks (p ¼ 0.015) but were similar at 6 weeks (p ¼ 0.689). Force-to-failure in knockouts was approximately 40% that of wild-type mice at 2 weeks (p ¼ 0.040) but similar at 6 weeks (p ¼ 0.735). Knockout bone was about 25% less stiff at 2 weeks but approximately 60% stiffer at 6 weeks (p ! 0.110). The absence of IL-6 during early fracture healing significantly reduced osteoclastogenesis and impaired callus strength. By 6 weeks, most histological and biomechanical parameters were similar to fractures in wild-type bone. Keywords: cytokines; interleukin-6; fracture healing Inflammation is a key component to both wound and bony healing responses. Leukocytosis is a part of this phenomenom and is integral to fracture healing.1-3 In particular, neutrophil infiltration is apparently allied with establishing chondrogenesis, a sentinel component of endochondral ossification. 4Cytokines are also involved in regulating the healing response. IL-1 plays a prominent role in the early response to injury, 5-7 exerting both proliferative [7][8][9][10] and catabolic effects. 11 It also stimulates the expression of IL-6 by osteoblasts. [12][13][14] There is a substantial body of research that suggest that IL-6 exerts effects on bone homeostasis and repair. IL-6 stimulates production of RANK ligand by osteoblasts which, in turn, catalyzes the formation of osteoclasts from peripheral blood monocytes.15 It was shown to induce differentiation of pre-osteoblasts, [16][17][18] inhibit nodule formation in bone culture, 19 and induce cathepsin B production by osteoblasts.20 During distraction osteogenesis, IL-6 is produced by osteoblasts, hemopoietic cells, and cells associated with the lengthening callus. 21 Murine models of fracture healing have shown elevations in IL-6 during intramembranous callus remodeling 22 as well as secondary bone remodeling associated with endochondral ossification. 23 Recently, Yang et al. 24 provided insight into the effects of IL-6 on fracture healing, noting an impairment of osteoclastogenesis. Similarly, Axmann et al. 25 showed that abrogating IL-6 receptor function also reduced osteoclast counts in a model of inflammatory (RA) bone erosion.Given the importance of the inflammatory response ...

In a simulated model of segmental clavicle fracture, a LCP provided more stiffness and less deflection than a low-contact dynamic compression plate.

No abstract

No abstract